Funds are requested to purchase an Agilent 6224 ESI-TOF mass spectrometer for molecular mass determination of proteins, peptides and small molecules for investigators at the University of Texas Health Science Center at San Antonio (UTHSCSA). The requested instrument will add valuable new capabilities to complement the existing Mass Spectrometry Laboratory (MSL) that has offered a wide range of proteomics services for many years. The impetus for initiating the effort to obtain an ESI-TOF mass spectrometer came from the establishment of a protein production facility in the UTHSCSA Department of Biochemistry that was set up to help investigators who require relatively large quantities of purified proteins for structural/biophysical studies but do not have the capacity in their own laboratory to generate the requisite protein. Initial exploration of ESI-TOF/MS instruments on the market took place in mid 2010. Because sufficient funds were not available at that time to purchase an instrument, representatives from Agilent approached the PI about the possibility of an on-site evaluation of an ESI-TOF/MS. An Agilent 6224 was installed in the MSL in summer 2011 and was integrated into the laboratory workflow several months later. The instrument has quickly become essential for support of many research projects, in particular, an NIH-funded investigation focusing on discovery of new natural products and synthetic compounds to provide more effective therapies for the treatment of cancer. Investigators who have had protein samples analyzed on the Agilent 6224 now recognize the substantial benefit of obtaining accurate and more comprehensive molecular mass information about their proteins as compared to the far less precise assessment provided by 1-D SDS PAGE and Western blotting. If this proposal is funded, the instrument will be made available in an open-access environment such that after proper training, staff/students from the users' laboratories will be able to conduc their own analyses with only minor supervision from MSL personnel. Analyses on the requested ESI-TOF mass spectrometer will be much more accurate, more cost-effective and with a faster turn-around time than is currently available through the MSL, and will be amenable to samples in a wider range of solution compositions. The agreement with Agilent is for a one-year evaluation, although it is hoped that the time can be extended until the review of this proposal is completed. The acquisition of an ESI-TOF mass spectrometer for molecular mass determination has the potential to positively impact a large number of NIH-funded investigations covering the full array of disciplines in biomedical research.